It is well known that, for many charged biopolymers of interest, e.g., single- and double-stranded DNA and sodium dodecyl sulfate (SDS)-denatured proteins, separations based on differences in electrophoretic mobilities in free solution are not possible [1,2]. Therefore, in order to effect electrophoretic separations of mixtures of these molecules, one has to employ a gel matrix which alters the frictional characteristics of these species in such a way as to introduce a molecular size dependence to electrophoretic mobility.
Heretofore, the gel matrix employed in capillary electrophoretic systems has generally been a solid gel, such as agarose gel, or cross-linked polymer matrix, such as a cross-linked polyacrylamide matrix. Such gels may be difficult to introduce into a capillary tube without bubbles or voids, and generally preclude reusing the tube.
More recently, capillary electrophoresis systems employing a polymer solution as separation medium have been disclosed. Co-owned U.S. patent application for "Nucleic Acid Fractionation by Counter-Migration Capillary Electrophoresis", Ser. No. 390,631, describes an electrophoresis system in which DNA fractionation occurs in a polymer solution which itself is migrating through the tube, by electro-osmotic flow, in a direction opposite to that of DNA movement in the gel. Co-owned U.S. patent application for "High-Viscosity Polymer Matrix and Methods", Ser. No. 472,045 discloses the use of a viscoelastic polymer solution as a substitute matrix for a cross-linked gel matrix in capillary electrophoresis.
Ideally, a polymer solution for separating a mixture of biopolymer molecules (e.g., DNA fragments or polypeptides) should have a selected mesh size for optimizing separation of the biopolymer molecules, and at the same time, have a minimum viscosity, to allow the solution to be readily drawn into and removed from the capillary tube. Heretofore, selecting polymers and polymer concentrations which provide a selected mesh size and low viscosity has been difficult. In particular, small mesh sizes suitable for fractionation of oligonucleotides, e.g., in DNA sequencing, has generally been achieved only at high polymer concentrations which also produce high solution viscosity. At the other end of the mesh size spectrum, where large polymers are required for achieving large mesh sizes, even relatively dilute polymer solutions can have relatively high viscosities.